This renewal application proposes to continue the cancer prevention programs of the University of Kentucky PRC, the only PRC dedicated to cancer prevention in rural Appalachia. Known locally as the Rural Cancer Prevention Center (RCPC), our past focus has been on the prevention (through vaccination) and early detection of cervical cancer. Through social marketing and planned outreach the RCPC has successfully leveraged the trust of rural people residing in the most economically depressed area of Appalachia (southeastern, KY). The proposed renewal offers plans to continue our community-based cancer prevention research, and to extend our programs to other regions of Appalachia, using sustainable models. Moreover, the previous research pertaining to cervical cancer prevention created a strong basis for testing a novel approach to community-based screening for colorectal cancer (CRC). Based on new screening technology, this approach will be effective and accessible to medically disenfranchised and under-served rural residents. The proposed plan has 5 general aims (A-E) and a specific research aim (F): A) Provide infrastructure and administrative services that support cancer prevention; B) Build community capacity and actively engage the community in partnerships for cancer prevention; C) Provide an efficient and effective communications network that ties cancer prevention activities together and disseminates health communication; D) Offer training and technical support to state and local agencies; E) Evaluate (process and outcome) all planned activities related to aims A-D; and F) Conduct an applied prevention research project that demonstrates the value of using community change agents to foster widespread adoption of annual colorectal cancer (CRC) screening with Fecal Immunochemical Test (FIT), followed by navigation to colonoscopy for those screening FIT-positive, and by an intervention program that promote annual repeat use of FIT. All six aims are inter-related; however, the final aim is a highly focused set of activities that occur in two phases: 1) the programs supporting this aim will be tested in Years 1-3, and 2) to benefit other rural Appalachian states, dissemination and implementation activities will be conducted in Years 4-5. Programs to be tested in Years 1-3 include 1) a community-based intervention featuring a Diffusion of Innovations model, standard RCPC outreach methods, and academic detailing for health care providers tested using a non-equivalent comparison design; this trial will end when 500 FIT specimens have been returned in the intervention health district, 2) a social network analysis (N = 64) used to provide interim feedback regarding key characteristics of effective change agents used in the diffusion model, 3) a navigation program (based on current RCPC practices for cervical cancer) that will be applied to people testing FIT-positive (N = 60), and 4) an internet-based program designed to foster annual repeat FIT screening tested using a randomized, controlled trial design (N = 220). Programs will be designed for optimal sustainability and dissemination/implementation potential.